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The 2005 Chawla-Rosenfeld Symposium on Developmental Therapeutics for Sarcoma

The 2005 Chawla-Rosenfeld Symposium on Developmental Therapeutics for Sarcoma. Introduction George D. Demetri, MD Dana-Farber Cancer Institute Harvard Medical School Ludwig Institute for Cancer Research. Developmental Therapeutics in Sarcomas.

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The 2005 Chawla-Rosenfeld Symposium on Developmental Therapeutics for Sarcoma

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  1. The 2005 Chawla-Rosenfeld Symposium on Developmental Therapeutics for Sarcoma Introduction George D. Demetri, MD Dana-Farber Cancer Institute Harvard Medical School Ludwig Institute for Cancer Research

  2. Developmental Therapeuticsin Sarcomas • Sarcomas are now recognized as important models for rational drug discovery and accelerated clinical development • Our field needs to expand this beyond targeted therapies for GIST

  3. Developmental Therapeuticsin Sarcomas • Today’s Topic:Expanding the preclinical and clinical collaborations to accelerate discovery and application in sarcoma research • Peter Houghton, PhD: cancer modeling • Rich Gorlick, MD: osteosarcoma frontiers • Antony Tolcher, MD: phase I to sarcomas • Chand Khanna, PhD, DVM:sarcoma research is going to the dogs

  4. The Question What is the next great target for a specific subtype of sarcoma?

  5. P P P P DOK SHC GRB-2 RAS-GAP SOS PI3K RAF-1 P P P P P P mTOR AKT MEK1/2 P BAD BCLXL 14-3-3 MYC 14-3-3 Which are the BEST Molecular Targetsin Sarcomas? Receptor Tyrosine Kinase SRC RAS-GTP RAS-GDP ? STAT1+3 SAPK BAD MAPK BCLXL Mitochondria Nucleus

  6. P P P P DOK SHC GRB-2 RAS-GAP SOS PI3K RAF-1 P P P P P P mTOR AKT MEK1/2 P BAD BCLXL 14-3-3 MYC 14-3-3 Which are the BEST Molecular Targetsin Sarcomas? Receptor Tyrosine Kinase Gleevec (Novartis) Sutent (Pfizer) SRC RAS-GTP RAS-GDP ? STAT1+3 SAPK BAD MAPK BCLXL Mitochondria Nucleus

  7. P P P P P P P P DOK SHC GRB-2 RAS-GAP SOS PI3K RAF-1 P P P P P P AKT mTOR MEK1/2 P BAD BCLXL 14-3-3 MYC 14-3-3 Molecular Targets in SARCOMAS Receptor Tyrosine Kinase BMS354825(Bristol-MS) Imatinib (Novartis) Sutent (Pfizer) SRC Zarnestra (JNJ) PI3kI (PIRAMED) RAS-GTP RAS-GDP ? STAT1+3 SORAFENIB (Bayer) SAPK RAD001(Novartis) CCI779 (Wyeth) AP23573 (ARIAD) BAD MAPK BCLXL Mitochondria Nucleus

  8. P P P P P P P P DOK SHC GRB-2 RAS-GAP SOS PI3K RAF-1 P P P P P P mTOR AKT MEK1/2 P BAD BCLXL 14-3-3 MYC 14-3-3 Molecular Targets in SARCOMAS Receptor Tyrosine Kinase BMS354825(Bristol-MS) Imatinib (Novartis) Sutent (Pfizer) SRC Zarnestra (JNJ) DRUG X PI3kI (PIRAMED) RAS-GTP RAS-GDP DRUG D DRUG C DRUG B ? STAT1+3 SORAFENIB (Bayer) DRUG Z SAPK RAD001(Novartis) CCI779 (Wyeth) AP23573 (ARIAD) BAD MAPK BCLXL DRUG Y Mitochondria Nucleus

  9. P P P P P P P P DOK SHC GRB-2 RAS-GAP SOS PI3K RAF-1 P P P P P P AKT mTOR MEK1/2 P BAD BCLXL 14-3-3 MYC 14-3-3 Molecular Targets in SARCOMAS Receptor Tyrosine Kinase BMS354825(Bristol-MS) Imatinib (Novartis) Sutent (Pfizer) SRC DRUG ZX DRUG ZN Zarnestra (JNJ) DRUG X DRUG X PI3kI (PIRAMED) DRUG ZN DRUG X RAS-GTP RAS-GDP DRUG ZN DRUG ZN DRUG X DRUG ZN DRUG ZN DRUG X DRUG D DRUG ZA DRUG ZN DRUG X DRUG ZN DRUG X DRUG C DRUG B DRUG ZN DRUG X DRUG ZN ? DRUG X DRUG ZN STAT1+3 DRUG X SORAFENIB (Bayer) DRUG ZN DRUG X DRUG ZN DRUG Z DRUG X DRUG ZN SAPK DRUG X RAD001(Novartis) CCI779 (Wyeth) AP23573 (ARIAD) DRUG X DRUG X DRUG Zy DRUG X BAD DRUG X MAPK DRUG X BCLXL DRUG ZN DRUG Y DRUG ZN DRUG ZN DRUG ZN Mitochondria Nucleus DRUG ZN DRUG ZZ

  10. Building Effective Collaborations with SARC and others to Answer These Important Questions International Sarcoma ResearchGroups Sarcoma Intergroups CTOS SARC US Govt Research Mechanisms Individual Investigators Patient Advocacy Groups

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